Search results for "tumorigenesis"
showing 10 items of 15 documents
MYC-driven epigenetic reprogramming favors the onset of tumorigenesis by inducing a stem cell-like state
2018
Breast cancer consists of highly heterogeneous tumors, whose cell of origin and driver oncogenes are difficult to be uniquely defined. Here we report that MYC acts as tumor reprogramming factor in mammary epithelial cells by inducing an alternative epigenetic program, which triggers loss of cell identity and activation of oncogenic pathways. Overexpression of MYC induces transcriptional repression of lineage-specifying transcription factors, causing decommissioning of luminal-specific enhancers. MYC-driven dedifferentiation supports the onset of a stem cell-like state by inducing the activation of de novo enhancers, which drive the transcriptional activation of oncogenic pathways. Furthermo…
[How some commensal bacteria would exacerbate colorectal carcinogenesis?].
2016
International audience; The gut microbiota maintains a relationship with its host with strong mutual benefits. Changes in the composition of the intestinal microbiota have been detected in colorectal cancer patients to the extent that it is now considered as a real contributing factor in this pathology. In this review, we focus on three commensal bacterial species, namely Bacteroides fragilis, Fusobacterium nucleatum, and Escherichia coli, which seem to emerge as pathogens and to contribute to colorectal carcinogenesis through their inflammatory and oncogenic properties.; Le microbiote intestinal entretient une relation mutualiste forte avec l’hôte. Depuis la mise en évidence de modificatio…
Silencing of hepatic fate-conversion factors induce tumorigenesis in reprogrammed hepatic progenitor-like cells
2016
Abstract Background Several studies have reported the direct conversion of mouse fibroblasts to hepatocyte-like cells with different degrees of maturation by expression of hepatic fate-conversion factors. Methods We have used a combination of lentiviral vectors expressing hepatic fate-conversion factors with Oct4, Sox2, Klf4, and Myc to convert mouse embryonic fibroblasts into hepatic cells. Results We have generated hepatic cells with progenitor-like features (iHepL cells). iHepL cells displayed basic hepatocyte functions but failed to perform functions characteristic of mature hepatocytes such as significant Cyp450 or urea cycle activities. iHepL cells expressed multiple hepatic-specific …
DNA methylation changes and somatic mutations as tumorigenic events in Lynch syndrome-associated adenomas retaining mismatch repair protein expression
2018
Background: DNA mismatch repair (MMR) defects are a major factor in colorectal tumorigenesis in Lynch syndrome (LS) and 15% of sporadic cases. Some adenomas from carriers of inherited MMR gene mutations have intact MMR protein expression implying other mechanisms accelerating tumorigenesis. We determined roles of DNA methylation changes and somatic mutations in cancer-associated genes as tumorigenic events in LS-associated colorectal adenomas with intact MMR. Methods: We investigated 122 archival colorectal specimens of normal mucosae, adenomas and carcinomas from 57 LS patients. MMR-deficient (MMR-D, n 49) and MMR-proficient (MMR-P, n 18) adenomas were of particular interest and were inter…
Deciphering genomic heterogeneity and the internal composition of tumour activities through a hierarchical factorisation model
2021
Genomic heterogeneity constitutes one of the most distinctive features of cancer diseases, limiting the efficacy and availability of medical treatments. Tumorigenesis emerges as a strongly stochastic process, producing a variable landscape of genomic configurations. In this context, matrix factorisation techniques represent a suitable approach for modelling such complex patterns of variability. In this work, we present a hierarchical factorisation model conceived from a systems biology point of view. The model integrates the topology of molecular pathways, allowing to simultaneously factorise genes and pathways activity matrices. The protocol was evaluated by using simulations, showing a hi…
The Friedreich's Ataxia protein frataxin modulates DNA base excision repair in prokaryotes and mammals
2010
DNA-repair mechanisms enable cells to maintain their genetic information by protecting it from mutations that may cause malignant growth. Recent evidence suggests that specific DNA-repair enzymes contain ISCs (iron–sulfur clusters). The nuclearencoded protein frataxin is essential for the mitochondrial biosynthesis of ISCs. Frataxin deficiency causes a neurodegenerative disorder named Friedreich's ataxia in humans. Various types of cancer occurring at young age are associated with this disease, and hence with frataxin deficiency. Mice carrying a hepatocyte-specific disruption of the frataxin gene develop multiple liver tumours for unresolved reasons. In the present study, we show that frata…
Classification or non-classification of substances with positive tumor findings in animal studies: Guidance by the German MAK commission
2019
One of the important tasks of the German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (known as the MAK Commission) is in the evaluation of a potential for carcinogenicity of hazardous substances at the workplace. Often, this evaluation is critically based on data on carcinogenic responses seen in animal studies and, if positive tumor responses have been observed, this will mostly lead to a classification of the substance under investigation into one of the classes for carcinogens. However, there are cases where it can be demonstrated with a very high degree of confidence that the tumor findings in the experimental animals are not relevant…
Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate
2021
Simple Summary Electric potential patterns across tissues are instructive for development, regeneration, and tumorigenesis because they can influence transcription, migration, and differentiation through biochemical and biomechanical downstream processes. Determining the origins of the spatial domains of distinct potential, which in turn decide anatomical features such as limbs, eyes, brain, and heart, is critical to a mature understanding of how bioelectric signaling drives morphogenesis. We studied theoretically how connexin proteins with different voltage-gated gap junction conductances can maintain multicellular regions at distinct membrane potentials. We analyzed a minimal model that i…
miR-205-5p-mediated downregulation of ErbB/HER receptors in breast cancer stem cells results in targeted therapy resistance
2015
AbstractThe ErbB tyrosine kinase receptor family has been shown to have an important role in tumorigenesis, and the expression of its receptor members is frequently deregulated in many types of solid tumors. Various drugs targeting these receptors have been approved for cancer treatment. Particularly, in breast cancer, anti-Her2/EGFR molecules represent the standard therapy for Her2-positive malignancies. However, in a number of cases, the tumor relapses or progresses thus suggesting that not all cancer cells have been targeted. One possibility is that a subset of cells capable of regenerating the tumor, such as cancer stem cells (CSCs), may not respond to these therapeutic agents. Accumula…
Molecular Mechanisms Leading from Periodontal Disease to Cancer
2022
Periodontitis is prevalent in half of the adult population and raises critical health concerns as it has been recently associated with an increased risk of cancer. While information about the topic remains somewhat scarce, a deeper understanding of the underlying mechanistic pathways promoting neoplasia in periodontitis patients is of fundamental importance. This manuscript presents the literature as well as a panel of tables and figures on the molecular mechanisms of Porphyromonas gingivalis and Fusobacterium nucleatum, two main oral pathogens in periodontitis pathology, involved in instigating tumorigenesis. We also present evidence for potential links between the RANKL–RANK signaling axi…